HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Srivastava, M. Articles by Maus, U. A. Search for Related Content PubMed PubMed Citation Articles by Srivastava, M. Articles by Maus, U. A.

The Inflammatory versus Constitutive Trafficking of Mononuclear Phagocytes into the Alveolar Space of Mice Is Associated with Drastic Changes in Their Gene Expression Profiles ¹

Mrigank Srivastava^*,¶, Steffen Jung, Jochen Wilhelm, Ludger Fink, Frank Bühling, Tobias Welte^¶, Rainer M. Bohle, Werner Seeger^*, Jürgen Lohmeyer^* and Ulrich A. Maus^2,*,¶

^* Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Department of Pathology, Justus-Liebig-University, Giessen, Germany; Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; Institute of Immunology, Otto-von-Guericke University, Magdeburg, Germany; and ^¶ Department of Pulmonary Medicine, Hannover School of Medicine, Hannover, Germany

Mononuclear phagocytes enter the lungs both constitutively to maintain alveolar macrophage and dendritic cell homeostasis, as well as during lung inflammation, where the role of these cells is less well defined. We used a transgenic mouse strain (CX₃CR1^+/GFP) that harbors a GFP label in circulating monocytes to identify and sort these cells from the vascular and alveolar compartments under both constitutive and acute lung inflammatory conditions. Using nylon arrays combined with real-time RT-PCR for gene expression profiling, we found that flow-sorted, highly purified mononuclear phagocytes recruited to acutely inflamed mouse lungs showed strongly up-regulated mRNA levels of the neutrophil chemoattractants KC, MIP-2, and IP-10, which contrasted with alveolar mononuclear phagocytes that immigrated in steady state. Similar observations were made for the lysosomal cathepsins B, L, and K being strongly up-regulated in mononuclear phagocytes upon recruitment to inflamed lungs but not during constitutive alveolar immigration. Inflammatory elicited mononuclear phagocytes also demonstrated significantly increased mRNA levels of the cytokine TNF- and the PRR-associated molecules CD14, TLR4, and syndecan-4. Together, inflammatory elicited mononuclear phagocytes exhibit strongly increased neutrophil chemoattractants, lysosomal proteases, and LPS signaling mRNA transcripts, suggesting that these cells may play a major role in acute lung inflammatory processes.

This article has been cited by other articles:

				M. Cabanski, J. Wilhelm, Z. Zaslona, M. Steinmuller, L. Fink, W. Seeger, and J. Lohmeyer Genome-wide transcriptional profiling of mononuclear phagocytes recruited to mouse lungs in response to alveolar challenge with the TLR2 agonist Pam3CSK4 Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L608 - L618. [Abstract] [Full Text] [PDF]

				A. M. Guth, W. J. Janssen, C. M. Bosio, E. C. Crouch, P. M. Henson, and S. W. Dow Lung environment determines unique phenotype of alveolar macrophages Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L936 - L946. [Abstract] [Full Text] [PDF]

				E. J. Cornish, B. J. Hurtgen, K. McInnerney, N. L. Burritt, R. M. Taylor, J. N. Jarvis, S. Y. Wang, and J. B. Burritt Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Independent Resistance to Aspergillus fumigatus in Alveolar Macrophages J. Immunol., May 15, 2008; 180(10): 6854 - 6867. [Abstract] [Full Text] [PDF]

				C. A Beamer and A. Holian Antigen-Presenting Cell Population Dynamics during Murine Silicosis Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 729 - 738. [Abstract] [Full Text] [PDF]

				W. von Wulffen, M. Steinmueller, S. Herold, L. M. Marsh, P. Bulau, W. Seeger, T. Welte, J. Lohmeyer, and U. A. Maus Lung Dendritic Cells Elicited by Fms-like Tyrosin 3-Kinase Ligand Amplify the Lung Inflammatory Response to Lipopolysaccharide Am. J. Respir. Crit. Care Med., November 1, 2007; 176(9): 892 - 901. [Abstract] [Full Text] [PDF]

				H. Hirakawa, R. A. Pierce, G. Bingol-Karakoc, C. Karaaslan, M. Weng, G.-P. Shi, A. Saad, E. Weber, T. J. Mariani, B. Starcher, et al. Cathepsin S Deficiency Confers Protection from Neonatal Hyperoxia-induced Lung Injury Am. J. Respir. Crit. Care Med., October 15, 2007; 176(8): 778 - 785. [Abstract] [Full Text] [PDF]

				C. Winter, K. Taut, F. Langer, M. Mack, D. E. Briles, J. C. Paton, R. Maus, M. Srivastava, T. Welte, and U. A. Maus FMS-Like Tyrosine Kinase 3 Ligand Aggravates the Lung Inflammatory Response to Streptococcus pneumoniae Infection in Mice: Role of Dendritic Cells J. Immunol., September 1, 2007; 179(5): 3099 - 3108. [Abstract] [Full Text] [PDF]

				C. Winter, K. Taut, M. Srivastava, F. Langer, M. Mack, D. E. Briles, J. C. Paton, R. Maus, T. Welte, M. D. Gunn, et al. Lung-Specific Overexpression of CC Chemokine Ligand (CCL) 2 Enhances the Host Defense to Streptococcus pneumoniae Infection in Mice: Role of the CCL2-CCR2 Axis J. Immunol., May 1, 2007; 178(9): 5828 - 5838. [Abstract] [Full Text] [PDF]

				U. A. Maus, M. Backi, C. Winter, M. Srivastava, M. K. Schwarz, T. Ruckle, J. C. Paton, D. Briles, M. Mack, T. Welte, et al. Importance of Phosphoinositide 3-Kinase {gamma} in the Host Defense against Pneumococcal Infection Am. J. Respir. Crit. Care Med., May 1, 2007; 175(9): 958 - 966. [Abstract] [Full Text] [PDF]

				C. H. P. Ong, Z. He, L. Kriazhev, X. Shan, R. G. E. Palfree, and A. Bateman Regulation of progranulin expression in myeloid cells Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1602 - R1612. [Abstract] [Full Text] [PDF]

				S. Kumar and R. Jack Invited review: Origin of monocytes and their differentiation to macrophages and dendritic cells Innate Immunity, October 1, 2006; 12(5): 278 - 284. [Abstract] [PDF]

				U. A. Maus, S. Janzen, G. Wall, M. Srivastava, T. S. Blackwell, J. W. Christman, W. Seeger, T. Welte, and J. Lohmeyer Resident Alveolar Macrophages Are Replaced by Recruited Monocytes in Response to Endotoxin-Induced Lung Inflammation Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 227 - 235. [Abstract] [Full Text] [PDF]